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Inhibitory role of long non‐coding RNA OIP5‐AS1 in rheumatoid arthritis progression through the microRNA‐448–paraoxonase 1–toll‐like receptor 3–nuclear factor κB axis
Author(s) -
Qing Pingying,
Liu Yi
Publication year - 2020
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/ep088608
Subject(s) - rheumatoid arthritis , paraoxonase , inflammation , arthritis , toll like receptor , microrna , immunology , tumor necrosis factor alpha , cancer research , receptor , medicine , biology , immune system , innate immune system , gene , oxidative stress , biochemistry
New FindingsWhat is the central question of this study? What are the functions of long non‐coding (lnc) RNA OIP5‐AS1 in development of rheumatoid arthritis inflammation and what is the molecular mechanism?What is the main finding and its importance? LncRNA OIP5‐AS1 mitigates rheumatoid arthritis progression through the competitive endogenous RNA network involving the miR‐448–paraoxonase 1 axis and through the inactivation of the toll‐like receptor 3–nuclear factor κB signalling pathway. This study may offer new ideas for molecularly based control of rheumatoid arthritis.Abstract Rheumatoid arthritis (RA) is an autoimmune disorder with dysregulation of long non‐coding RNAs (lncRNAs) possibly involved. This study aimed to inquire into the roles of lncRNA OIP5‐AS1 in RA progression. A rat model of RA was induced. Overexpression of OIP5‐AS1 was introduced in the model rats, and the changes in paw swelling, RA severity and the inflammatory factors interleukin (IL)‐1β, IL‐10, IL‐6 and tumour necrosis factor α were measured. Fibroblast‐like synoviocytes (FLSs) from RA patients were collected for in vitro experiments. A gain‐ and loss‐of function study of OIP5‐AS1, miR‐448 and paraoxonase 1 (PON1) was performed to explore their roles in RA‐FLS growth, apoptosis and inflammation. A toll‐like receptor 3 (TLR3)‐specific agonist, polyinosine‐polycytidylic acid, or a nuclear factor κB (NF‐κB)‐specific antagonist, QNZ, was administrated in RA‐FLSs. Consequently, overexpression of OIP5‐AS1 reduced the symptom severity and the levels of inflammatory factors in RA rats. OIP5‐AS1 could bind to miR‐448 to up‐regulate PON1 expression. Further overexpression of miR‐448 reversed the effects of OIP5‐AS1, while overexpression of PON1 inhibited RA‐FLS growth and inflammation. In addition, TLR3 activation promoted RA progression. To conclude, this study evidenced that lncRNA OIP5‐AS1 may mitigate RA progression through the miR‐448–PON1 axis and through the inactivation of the TLR3–NF‐κB signalling pathway.